tbuckley/cabot-search huggingface dataset:
<scp>Health‐related</scp> quality of life outcomes in <scp>PARAGON‐HF</scp>
Authors: Alvin Chandra, Carisi A. Polanczyk, Brian L. Claggett, Muthiah Vaduganathan, Milton Packer, Martin P. Lefkowitz, Jean L. Rouleau, Jiankang Liu, Victor C. Shi, Heike Schwende, Michael R. Zile, Akshay S. Desai, Marc A. Pfeffer, John J.V. McMurray, Scott D. Solomon, Eldrin F. Lewis
Journal: European Journal of Heart Failure (2022)

Abstract Aims Heart failure (HF) is associated with poor health‐related quality of life (HRQL). Patients with HF with preserved ejection fraction (HFpEF) have similar HRQL impairment as those with reduced ejection fraction. This study describes the impact of sacubitril/valsartan on HRQL in patients with HFpEF enrolled in the PARAGON‐HF trial. Methods and results Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQol (EQ‐5D) at randomization, 4, 8 months, and annually thereafter. Changes in HRQL scores were evaluated using repeated measures models adjusted for treatment, baseline values and region. The pre‐specified principal efficacy assessment was at 8 months at which time patients randomized to sacubitril/valsartan had borderline higher KCCQ clinical summary score (CSS) with least squares mean (LSM) adjusted difference of 1.0 (95% confidence interval [CI] 0.0, 2.1; p = 0.051). Including all visits up to 36 months, the LSM difference in KCCQ‐CSS favoured sacubitril/valsartan with average adjusted difference of 1.1 (95% CI 0.1, 2.0; p = 0.034). Patients treated with sacubitril/valsartan had greater odds of clinically meaningful improvement (≥5‐point increase) in KCCQ‐CSS (odds ratio 1.31; 95% CI 1.06, 1.61) at 8 months. At 8 months, there was no significant difference in the EQ visual analogue scale between the treatment arms, but sacubitril/valsartan was associated with higher EQ‐5D utility score (US‐based) with LSM adjusted difference of 0.01 (95% CI 0.00, 0.02; p = 0.019). Conclusion Compared with valsartan, sacubitril/valsartan had a borderline benefit on KCCQ‐CSS at 8 months in patients with HFpEF. This benefit became more significant when data from all visits up to 36 months were included. This modest overall benefit was also supported by greater odds of patients reporting a clinically meaningful improvement in HRQL with sacubitril/valsartan.
Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer’s disease
Authors: Alena Salasova, Giulia Monti, Olav M. Andersen, Anders Nykjaer
Journal: Molecular Neurodegeneration (2022)

Abstract The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer’s disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Re: Khyati Meghani, Lauren Folgosa Cooley, Bonnie Choy, et al. First-in-human Intravesical Delivery of Pembrolizumab Identifies Immune Activation in Bladder Cancer Unresponsive to Bacillus Calmette-Guérin. Eur Urol. 2022;82:602–10
Authors: Ryan L Steinberg, Michael A O'Donnell, Vignesh T Packiam
Journal: European Urology (2022)
Incorporating Prostate-specific Membrane Antigen Positron Emission Tomography in Management Decisions for Men with Newly Diagnosed or Biochemically Recurrent Prostate Cancer
Authors: Laura Bukavina, Amy N. Luckenbaugh, Michael S. Hofman, Tom Hope, Sophia C. Kamran, Declan G. Murphy, Kosj Yamoah, Piet Ost
Journal: European Urology (2022)
Biodegradable magnesium materials regulate ROS-RNS balance in pro-inflammatory macrophage environment
Authors: Maria P. Kwesiga, Amani A. Gillette, Fatemeh Razaviamri, Margaret E. Plank, Alexia L. Canull, Zachary Alesch, Weilue He, Bruce P. Lee, Roger J. Guillory
Journal: Bioactive Materials (2022)

The relationship between reactive oxygen and nitrogen species (ROS-RNS) secretion and the concomitant biocorrosion of degradable magnesium (Mg) materials is poorly understood. We found that Mg foils implanted short term in vivo (24 h) displayed large amounts of proinflammatory F4/80+/iNOS + macrophages at the interface. We sought to investigate the interplay between biodegrading Mg materials (98.6% Mg, AZ31 & AZ61) and macrophages (RAW 264.7) stimulated with lipopolysaccharide (RAW 264.7LPS) to induce ROS-RNS secretion. To test how these proinflammatory ROS-RNS secreting cells interact with Mg corrosion in vitro, Mg and AZ61 discs were suspended approximately 2 mm above a monolayer of RAW 264.7 cells, either with or without LPS. The surfaces of both materials showed acute (24 h) changes when incubated in the proinflammatory RAW 264.7LPS environment. Mg discs incubated with RAW 264.7LPS macrophages showed greater corrosion pitting, while AZ61 showed morphological and elemental bulk product changes via scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX). X-ray photoelectron spectroscopy (XPS) analysis showed a reduction in the Ca/P ratio of the surface products for AZ61 disc incubated with RAW 264.7LPS, but not the Mg discs. Moreover, RAW 264.7LPS macrophages were found to be more viable in the acute biodegradative environment generated by Mg materials, as demonstrated by calcein-AM and cleaved (active) caspase-3 staining (CC3). LPS stimulation caused an increase in ROS-RNS, and a decrease in antioxidant peroxidase activity. Mg and AZ61 were found to change this ROS-RNS balance, independently of physiological antioxidant mechanisms. The findings highlight the complexity of the cellular driven acute inflammatory responses to different biodegradable Mg, and how it can potentially affect performance of these materials.
Randomised controlled trials utilising<i>F</i><sub>ENO</sub>to manage asthma: is it time to acknowledge that “one size does not fit all”?
Authors: Helen Petsky
Journal: European Respiratory Journal (2022)

<b>Murphy and co-workers provide further information on the tailoring of asthma treatment based on <i>F</i><sub>ENO</sub> for pregnant mothers and perinatal outcomes; however, a composite algorithm may be needed for RCTs utilising <i>F</i><sub>ENO</sub></b>https://bit.ly/3Bw1vO6
Cancer situation in China: what does the China cancer map indicate from the first national death survey to the latest cancer registration?
Authors: Ruimei Feng, Qingling Su, Xiaoyin Huang, Til Basnet, Xin Xu, Weimin Ye
Journal: Cancer Communications (2022)

Abstract Background Over the past four decades, the Chinese government has conducted three surveys on the distribution of causes of death and built cancer registration. In order to shine a new light on better cancer prevention strategies in China, we evaluated the profile of cancer mortality over the forty years and analyzed the policies that have been implemented. Methods We described spatial and temporal changes in both cancer mortality and the ranking of major cancer types in China based on the data collected from three national surveys during 1973‐1975, 1990‐1992, 2004‐2005, and the latest cancer registration data published by National Central Cancer Registry of China. The mortality data were compared after conversion to age‐standardized mortality rates based on the world standard population (Segi's population). The geographical distribution characteristics were explored by marking hot spots of different cancers on the map of China. Results From 1973 to 2016, China witnessed an evident decrease in mortality rate of stomach, esophageal, and cervical cancer, while a gradual increase was recorded in lung, colorectal, and female breast cancer. A slight decrease of mortality rate has been observed in liver cancer since 2004. Lung and liver cancer, however, have become the top two leading causes of cancer death for the last twenty years. From the three national surveys, similar profiles of leading causes of cancer death were observed among both urban and rural areas. Lower mortality rates from esophageal and stomach cancer, however, have been demonstrated in urban than in rural areas. Rural areas had similar mortality rates of the five leading causes of cancer death with the small urban areas in 1973‐1975. Additionally, rural areas in 2016 also had approximate mortality rates of the five leading causes with urban areas in 2004‐2005. Moreover, stomach, esophageal, and liver cancer showed specific geographical distributions. Although mortality rates have decreased at most of the hotspots of these cancers, they were still higher than the national average levels during the same time periods. Conclusions Building up a strong primary public health system especially among rural areas may be one critical step to reduce cancer burden in China.
Repeated photodynamic therapy mediates the abscopal effect through multiple innate and adaptive immune responses with and without immune checkpoint therapy
Authors: Jenny Lou, Masato Aragaki, Nicholas Bernards, Tess Chee, Alexander Gregor, Yoshihisa Hiraishi, Tsukasa Ishiwata, Chelsea Leung, Lili Ding, Shinsuke Kitazawa, Takamasa Koga, Yuki Sata, Hiroyuki Ogawa, Juan Chen, Tatsuya Kato, Kazuhiro Yasufuku, Gang Zheng
Journal: Biomaterials (2022)
Real-world clinical outcome of cefiderocol for treatment of multidrug-resistant non-fermenting, gram negative bacilli infections: a case series
Authors: Baptiste Hoellinger, Célestine Simand, Katy Jeannot, Carlos Garijo, Mircea Cristinar, Fanny Reisz, François Danion, Axel Ursenbach, Nicolas Lefebvre, Pierre Boyer, Yves Hansmann, Antoine Studer, Frédéric Schramm, Yvon Ruch
Journal: Clinical Microbiology and Infection (2022)
Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease
Authors: Paul Martin, Ahmed A. Awan, Marina C. Berenguer, Annette Bruchfeld, Fabrizio Fabrizi, David S. Goldberg, Jidong Jia, Nassim Kamar, Rosmawati Mohamed, Mário Guimarães Pessôa, Stanislas Pol, Meghan E. Sise, Ethan M. Balk, Craig E. Gordon, Gaelen Adam, Michael Cheung, Amy Earley, Michel Jadoul
Journal: Kidney International (2022)

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.
Epidemiological investigation of a case of malaria in a non-endemic area, Campo de Gibraltar, Cadiz, Spain, January 2022
Authors: Boris Verona Mesia, Nuria López-Ruiz, Enric Duran-Pla
Journal: Eurosurveillance (2022)

We describe a non-imported malaria case reported in January 2022 in Campo de Gibraltar and the investigations by local public health authorities to identify the transmission mechanism and subsequent measures to prevent local transmission. Vector transmission, parenteral transmission, airport malaria, and imported malaria were ruled out. No clear mechanism of transmission was identified. The most probable cause was a hospital-acquired infection since the case was admitted to hospital at the same time as a case of imported Plasmodium falciparum malaria.
Large increase in bloodstream infections with carbapenem-resistant Acinetobacter species during the first 2 years of the COVID-19 pandemic, EU/EEA, 2020 and 2021
Authors: Pete Kinross, Carlo Gagliotti, Hanna Merk, Diamantis Plachouras, Dominique L Monnet, Liselotte Diaz Högberg
Journal: Eurosurveillance (2022)

Recent data from the European Antimicrobial Resistance Surveillance Network (EARS-Net) show a large increase of +57% in Acinetobacter species bloodstream infections in the European Union and European Economic Area in the first years of the COVID-19 pandemic (2020-2021) compared with 2018-2019. Most were resistant to carbapenems, from intensive care units, and in countries with ≥ 50% carbapenem resistance in Acinetobacter spp. in 2018-2019. This highlights the requirement for reinforced Acinetobacter preparedness and infection prevention and control in Europe.
Detection of 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae in the United Kingdom, December 2021 to June 2022
Authors: Michaela Day, Rachel Pitt, Nisha Mody, John Saunders, Rupa Rai, Achyuta Nori, Hannah Church, Sarah Mensforth, Helen Corkin, Jacqueline Jones, Preneshni Naicker, Wazirzada M Khan, Rebecca Thomson Glover, Kalani Mortimer, Chloe Hylton, Elizabeth Moss, Thomas Joshua Pasvol, Ania Richardson, Suzy Sun, Neil Woodford, Hamish Mohammed, Katy Sinka, Helen Fifer
Journal: Eurosurveillance (2022)

Between December 2021 and June 2022, 10 cases of ceftriaxone-resistant Neisseria gonorrhoeae (ST8123; n = 8) were detected in the United Kingdom, compared with nine cases during the previous 6 years. Most of these cases were associated with travel from the Asia-Pacific region; all were heterosexual people, with most in their 20s. Although all cases were successfully treated, not all partners of cases could be traced, and there is a risk of further transmission of ceftriaxone-resistant gonococcal infection within the UK.
A step forward in antibiotic use and resistance monitoring: a quarterly surveillance system pilot in 11 European Union/European Economic Area countries, September 2017 to May 2020
Authors: Germán Peñalva, Paloma Crespo-Robledo, Mari Molvik, Antonio López-Navas, Oliver Kacelnik, José Miguel Cisneros
Journal: Eurosurveillance (2022)

BackgroundSurveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU) in Europe is currently annual.AimTo study the feasibility and scalability of a quarterly AMR/AMU surveillance system in the European Union/European Economic Area (EU/EEA).MethodsWe conducted a longitudinal study within the scope of the EU-JAMRAI project. Seventeen partners from 11 EU/EEA countries prospectively collected 41 AMU and AMR indicators quarterly from September 2017 to May 2020 for the hospital sector (HS) and primary care (PC). Descriptive statistics and coefficients of variation (CV) analysis were performed.ResultsData from 8 million hospital stays and 45 million inhabitants per quarter were collected at national (n = 4), regional (n = 6) and local (n = 7) levels. Of all partners, five were able to provide data within 3 months after each preceding quarter, and eight within 3-6 months. A high variability in AMU was found between partners. Colistin was the antibiotic that showed the highest CV in HS (1.40; p < 0.0001). Extended-spectrum beta-lactamase-producing Escherichia coli presented the highest incidence in HS (0.568 ± 0.045 cases/1,000 bed-days per quarter), whereas ciprofloxacin-resistant E. coli showed the highest incidence in PC (0.448 ± 0.027 cases/1,000 inhabitants per quarter). Barriers and needs for implementation were identified.ConclusionThis pilot study could be a first step towards the development of a quarterly surveillance system for AMU and AMR in both HS and PC in the EU/EEA. However, committed institutional support, dedicated human resources, coordination of data sources, homogeneous indicators and modern integrated IT systems are needed first to implement a sustainable quarterly surveillance system.
Increasing number of cases and outbreaks caused by Candida auris in the EU/EEA, 2020 to 2021
Authors: Anke Kohlenberg, Dominique L Monnet, Diamantis Plachouras
Journal: Eurosurveillance (2022)

The number of cases of Candida auris infection or carriage and of countries reporting cases and outbreaks increased in the European Union and European Economic Area during 2020 and 2021. Eight countries reported 335 such cases in 2020 and 13 countries 655 cases in 2021. Five countries experienced outbreaks while one country reported regional endemicity. These findings highlight the need for adequate laboratory capacity and surveillance for early detection of C. auris and rapid implementation of control measures.
Outbreak of imported diphtheria with Corynebacterium diphtheriae among migrants arriving in Germany, 2022
Authors: Franziska Badenschier, Anja Berger, Alexandra Dangel, Annika Sprenger, Bernhard Hobmaier, Claudia Sievers, Henrieke Prins, Achim Dörre, Christiane Wagner-Wiening, Wiebe Külper-Schiek, Ole Wichmann, Andreas Sing
Journal: Eurosurveillance (2022)

From July 2022, cases of imported diphtheria with toxigenic Corynebacterium diphtheriae remarkably increased among migrants arriving in Germany. Up to 30 September 2022, 44 cases have been reported to the national public health institute, all laboratory-confirmed, male, and mainly coming from Syria (n = 21) and Afghanistan (n = 17). Phylogeny and available journey information indicate that most cases (n = 19) were infected along the Balkan route. Active case finding, increased laboratory preparedness and epicentre localisation in countries along this route are important.
Parallel evolution of amphioxus and vertebrate small-scale gene duplications
Authors: Marina Brasó-Vives, Ferdinand Marlétaz, Amina Echchiki, Federica Mantica, Rafael D. Acemel, José L. Gómez-Skarmeta, Diego A. Hartasánchez, Lorlane Le Targa, Pierre Pontarotti, Juan J. Tena, Ignacio Maeso, Hector Escriva, Manuel Irimia, Marc Robinson-Rechavi
Journal: Genome biology (2022)

Abstract Background Amphioxus are non-vertebrate chordates characterized by a slow morphological and molecular evolution. They share the basic chordate body-plan and genome organization with vertebrates but lack their 2R whole-genome duplications and their developmental complexity. For these reasons, amphioxus are frequently used as an outgroup to study vertebrate genome evolution and Evo-Devo. Aside from whole-genome duplications, genes continuously duplicate on a smaller scale. Small-scale duplicated genes can be found in both amphioxus and vertebrate genomes, while only the vertebrate genomes have duplicated genes product of their 2R whole-genome duplications. Here, we explore the history of small-scale gene duplications in the amphioxus lineage and compare it to small- and large-scale gene duplication history in vertebrates. Results We present a study of the European amphioxus ( Branchiostoma lanceolatum ) gene duplications thanks to a new, high-quality genome reference. We find that, despite its overall slow molecular evolution, the amphioxus lineage has had a history of small-scale duplications similar to the one observed in vertebrates. We find parallel gene duplication profiles between amphioxus and vertebrates and conserved functional constraints in gene duplication. Moreover, amphioxus gene duplicates show levels of expression and patterns of functional specialization similar to the ones observed in vertebrate duplicated genes. We also find strong conservation of gene synteny between two distant amphioxus species, B. lanceolatum and B. floridae , with two major chromosomal rearrangements. Conclusions In contrast to their slower molecular and morphological evolution, amphioxus’ small-scale gene duplication history resembles that of the vertebrate lineage both in quantitative and in functional terms.
Towards elucidating disease-relevant states of neurons and glia by CRISPR-based functional genomics
Authors: Kun Leng, Martin Kampmann
Journal: Genome Medicine (2022)

Abstract Our understanding of neurological diseases has been tremendously enhanced over the past decade by the application of new technologies. Genome-wide association studies have highlighted glial cells as important players in diseases. Single-cell profiling technologies are providing descriptions of disease states of neurons and glia at unprecedented molecular resolution. However, significant gaps remain in our understanding of the mechanisms driving disease-associated cell states, and how these states contribute to disease. These gaps in our understanding can be bridged by CRISPR-based functional genomics, a powerful approach to systematically interrogate gene function. In this review, we will briefly review the current literature on neurological disease-associated cell states and introduce CRISPR-based functional genomics. We discuss how advances in CRISPR-based screens, especially when implemented in the relevant brain cell types or cellular environments, have paved the way towards uncovering mechanisms underlying neurological disease-associated cell states. Finally, we will delineate current challenges and future directions for CRISPR-based functional genomics to further our understanding of neurological diseases and potential therapeutic strategies.
Little evidence supports gabapentinoid use in bipolar disorder or insomnia
Authors: Helen Saul, Deniz Gursul, Samantha Cassidy, Paul Harrison
Journal: BMJ (2022)

The study Hong JSW, Atkinson LZ, Al-Juffali N, et al. Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: systematic review, meta-analysis, and rationale. Mol Psychiatry 2022;27:1339-49. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/review-finds-little-evidence-support-gabapentinoid-use-bipolar-disorder-or-insomnia/